Recent Advances in Treating HIV-Hepatitis C Coinfection

A review in Future Virology discussed in detail the latest treatment options for HIV—HCV coinfection, related pharmacological issues, and the potential risks practitioners should consider when selecting individualized regimens.

Hepatitis C virus (HCV) infection is a prevalent global health concern, affecting 150 million people worldwide and 5.2 million individuals in the United States. WHO estimates the annual death toll from HCV-related diseases to exceed 350,000.

Authors noted that about 25% of people infected with HIV in the United States also are infected with HCV, and the coinfection rate for injection-drug users is approaching 100%.

Compared with HCV monoinfection, HIV—HCV coinfection is associated with a threefold greater risk of hepatic fibrosis progression, leading to cirrhosis and liver cancer. This risk is especially prominent among those whose HIV is not effectively managed.

To illustrate the difference, authors noted that cirrhosis or end-stage liver disease can develop in 6 to 10 years for coinfected patients, whereas it may take 20 to 30 years for HCV monoinfected patients.

HIV-HCV Treatment Advances with Next Generation Antivirals

Compared with older interferon-based therapies, new direct-acting antivirals (DAAs) offer increased efficacy, shorter treatment durations, and less severe side effects, the review said. Multiple first-line DAA therapeutic options recently have been approved, showing equivalent sustained virologic response (SVR) rates for HIV—HCV coinfected patients and HCV monoinfected patients.

Recently approved all-oral DAA-based regimens offer tremendous benefits for patients with HIV—HCV, according to the review, because the simplicity of a daily pill promotes medication adherence and their SVR rates, >90% in most cases, and adverse event profiles are similar for HIV–HCV coinfected and HCV monoinfected populations.

Important Considerations for Treating HIV—HCV Coinfection

Authors reviewed in detail the different mechanisms of action and potential pharmacologic interactions associated with DAA-based combination regimens used to treat HIV—HCV coinfection.

The researchers stressed that complex drug—drug interactions are a special concern for coinfected patients, partly because their disease state impacts the gut and liver, where metabolism takes place, and also because the chronic inflammation that can result from viral infection affects many body processes, including metabolism.

Healthcare providers should have a firm understanding of the clinical pharmacology at play, including metabolism and transporter effects, when selecting HIV—HCV regimens.

For example, the review noted that many DAA agents interact with metabolizing enzymes and membrane transporters; and many antiretrovirals are substrates, inhibitors, and inducers of metabolizing enzymes and substrates and/or inhibitors of membrane transporters.

Antiretroviral agents with minimal drug—drug interactions—such as, integrase strand transfer inhibitors raltegravir or dolutegravir, or the nonnucleoside reverse transcriptase inhibitor, rilpivirine—tend to be good choices for patients also receiving HCV therapy. Authors warned about a possible negative interaction between ledipasivr + tenofovir regimens and a pharmacokinetic enhancer like ritonavir or cobicistat.

The review warned that both women and men of reproductive age should use contraception and be advised of the risks associated with ribavirin (RBV), known to cause teratogenesis and embryocidal effects. It is listed as a pregnancy category X drug and remains in the bloodstream up to 4 weeks, and the potential for men to transmit RBV through fertilization remains unknown.

Authors also presented clinical evidence that a certain combination of HIV and HCV therapies might affect patients of African descent differently than others. In 1 study of HIV—HCV coinfected patients, 331 people receiving antiretroviral therapy (ART) regimens of tenofovir/emtricitabine + either efavirenz, raltegravir, or rilpivirine were given an HCV regimen of ledipasvir + sofosbuvir for 12 weeks. Individuals of African descent using these regimens achieved significantly lower SVR at 12 weeks and represented the entire subset (10 of 331) that experienced relapse.

Other studies discussed in this review demonstrated that HIV—HCV coinfected patients experience a higher incidence of adverse events in the course of some combination antiviral therapies, compared with monoinfected patients. The most common adverse reactions were fatigue, insomnia, headache, and irritability.

The review went on to discuss a multitude of other considerations and suggestions, stressing that pharmacogenetics is likely to be an important factor in HIV—HCV therapy. Authors summarized current research on the relationships between certain genotypes and novel DAAs, and reminded readers that the American Association for the Study of Liver Diseases recommends HCV genotyping to select antiviral regimen and treatment duration and to predict response.

In addition to the most common side effects already discussed, care providers should watch for, prevent, and/or mediate adverse reactions such as: gastrointestinal distress, nausea, or diarrhea; dry, itchy skin or rash; blisters or conjunctivitis; anemia (especially with RBV); joint pain; and muscle pain.